Project Summary/Abstract Pulmonary physicians and respiratory researchers define respiratory health as the absence of lung disease. This simplistic definition has limited the development of a robust approach to the prevention of lung disease. Because of the absence of adult life-course studies focused primarily on lung health, the intermediate phenotypes of impaired lung health (which exist on a continuum between ideal lung health and lung disease) have not been well-defined. There is a critical need to identify modifiable risk factors and biomarkers for impaired lung health that will allow clinicians to recognize impaired lung health and intervene before chronic lung disease develops. We will leverage the national infrastructure of the American Lung Association?s (ALA) Airways Clinical Research Centers (ACRC) to form the first national cohort of adults focused on respiratory health. We will recruit 4000 community-dwelling adults aged 25-35 from 17 metropolitan regions across the U.S. for the purpose of defining lung health and developing targets to intercept chronic lung disease at its earliest stages. Our long-term goal is to determine early adulthood factors that influence risk for future lung disease through detailed assessments of exposures (environmental, socio-behavioral, and occupational) and responses (physiologic, imaging-based, and biological including the nasal epithelial transcriptome). In this initial baseline evaluation, informed by our preliminary data indicating impaired lung health (lower lung function, self-report of respiratory symptoms, lung injury on chest CT scan) precedes the development of chronic lung disease, we will test several hypotheses regarding the risk factors and manifestations of impaired lung health in young adults through the following specific aims: (1) Determine whether modifiable exposures and risk factors (lifetime air pollution, potentially noxious inhalational exposures such as marijuana and e-cigarettes, reduced physical activity) are associated with lower lung function and greater burden of respiratory symptoms in young adults; (2) Determine whether CT-measurements of small airway and parenchymal lung injury are associated with lower lung function and greater burden of respiratory symptoms in young adults; (3) Determine the association between the nasal respiratory epithelial transcriptome and selected blood biomarkers, CT- measured small airway abnormality and parenchymal lung injury in young adults. We will test the hypotheses that (1) lifetime exposure to air pollution and other inhalational exposures (e.g. e-cigarettes and marijuana) are associated with impaired lung health; (2) novel imaging measurements are associated with impaired lung health; and (3) respiratory compartment-specific (nasal epithelial transciptome) and blood based biomarkers provide insight into the biologic underpinnings of impaired lung health. These studies will describe the divergence between respiratory health and disease and provide a platform for health promotion and the primary prevention of lung disease.